With the emergence of obesity treatments that can be taken as pills instead of injections, interest in obesity treatment is growing even hotter in Korea. The obesity treatments known as “Wegovy” and “Mounjaro” belong to the glucagon-like peptide-1 (GLP-1) class. GLP-1-based obesity treatments work by increasing the secretion of insulin, a hormone that regulates blood sugar, and suppressing glucagon secretion, thereby suppressing appetite and lowering blood glucose levels.

A Korean research team has discovered that, instead of using drugs that regulate hormones, there is a “switch” that blocks the formation of fat altogether. This presents a new possibility for more precise control of obesity and metabolic diseases in the future.

KAIST announced on the 25th that a research team led by Professors Dae-Sik Lim and Ju-Kyeong Kang of the Department of Biological Sciences had identified that YAP·TAZ, the key regulators in the “Hippo signaling pathway,” function as differentiation-suppressing switches during the adipocyte differentiation process. The Hippo signaling pathway controls when cells grow and when they stop dividing and begin to differentiate. It is a kind of cellular traffic control system. Adipocyte differentiation is the process in which precursor cells, the stage before differentiation into fat, transform into mature fat cells. The research findings were published on the 14th in the international journal Science Advances.

Metabolic diseases such as obesity and fatty liver are rapidly increasing worldwide. Although obesity treatments and similar drugs are showing effectiveness, methods to fundamentally regulate the process by which fat is formed remain limited. In particular, once adipocytes are created, they do not easily decrease in number. This is why weight loss through dieting often falls short of what is intended.

Cell differentiation is not simply a matter of genes being turned on or off. It is a complex process in which multiple genes act in an integrated manner. To examine this complex process, the research team tracked the entire process by which precursor cells differentiate into adipocytes. The team used technology that can simultaneously analyze not only gene expression but also changes in the epigenome. The epigenome refers to DNA base sequences that change due to intrinsic genome regulation, aging, or environmental changes.

The analysis showed that when YAP·TAZ were activated, the mechanism that confirms cells as adipocytes did not function. The entire process of differentiation into adipocytes was also suppressed.

In particular, through single-cell analysis of adipose tissue, the research team identified “VGLL3 (Vestigial Like Family Member 3)” as a new target gene of YAP·TAZ. They found that VGLL3 indirectly regulates the entire process of adipocyte differentiation. This means that YAP·TAZ, the key regulators in the Hippo signaling pathway, play an important role in determining when and how many adipocytes are generated.

Professor Lim stated, “This study is the first to demonstrate that adipocyte differentiation is precisely controlled at the epigenomic level, beyond simple gene regulation,” adding, “In the long term, it will serve as a foundation for developing personalized therapeutic strategies for patients with metabolic diseases such as obesity and fatty liver.”

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